PARKINSON’SDISEASE2014 ADVANCING RESEARCH, IMPROVING LIVES PROGRAM MATERIALS Sponsored by: January 6 – 7, 2014 Natcher Conference Center National Institutes of Health Bethesda, MD About our cover: The program cover image is a stylized version of the Parkinson’s Disease Motor-Related Pattern (PDRP), an abnormal pattern of regional brain function observed in MRI studies which shows increased metabolism indicated by red in some brain regions (pallidothalamic, pontine, and motor cortical areas), and decreased metabolism indicated by blue in others (associated lateral premotor and posterior parietal areas). Original image used with permission of David Eidelberg, M.D. For further information see: Hirano et al., Journal of Neuroscience 28 (16): 4201-4209. Welcome Message from Dr. Story C. Landis Welcome to the National Institute of Neurological Disorders and Stroke (NINDS) conference, “Parkinson’s Disease 2014: Advancing Research, Improving Lives.” Remarkable new discoveries and technological advances are rapidly changing the way we study the biological mechanisms of Parkinson’s disease, identify paths to improved treatments, and design effective clinical trials. Elucidating mechanisms and developing and testing effective interventions require a diverse set of approaches and perspectives. The NINDS has organized this conference with the primary goal of seeking consensus on, and prioritizing, research recommendations spanning clinical, translational, and basic Parkinson’s disease research that we support. We have assembled a stellar and dedicated group of session chairs and panelists who have worked collaboratively to identify emerging research opportunities in Parkinson’s research. While we have divided our working groups into three main research areas, we expect each will inform the others over the course of the next two days, and we look forward to both complementary and unique perspectives. On behalf of the NINDS, I would like to thank the many people who helped to make this conference possible, especially conference Chair Thomas Montine, Session Co-Chairs Randall Bateman, John Dunlop, Steven Finkbeiner, Virginia Lee, Harry Orr, and Andrew Siderowf, and all the panel members who generously dedicated many hours of their time to this effort and graciously navigated an extraordinarily condensed planning timeline due to the 2013 shutdown of the federal government. I also want to thank the representatives from academia, industry, government, and non-profit and advocacy organizations who are joining us to share their perspectives and to reflect upon how the recommendations during the next two days might be impacted by and have impact on their research programs. It is our hope that this meeting will foster continued conversation with our partner organizations and facilitate achievement of our common goal to find the causes, improved treatments, and one day a cure, for Parkinson’s disease. Our expectation is that the dynamic recommendations that result from this conference will catalyze advances in Parkinson’s research here at the NIH and beyond. Thank you for your active participation. Agenda January 6, 2014 (Day 1) 8:00 a.m. Welcome and Introduction Story C. Landis, PhD Director, NINDS 8:15 a.m. Meeting Goals Thomas J. Montine, MD, PhD Alvord Professor and Chair Department of Pathology, University of Washington 8:30 a.m. Bringing Emerging Science to People with Parkinson’s Disease through Clinical Research Session Chairs: Randall Bateman, MD, and Andrew Siderowf, MD NINDS Liaisons: Wendy Galpern, MD, PhD, and Walter Koroshetz, MD Introduction Randall Bateman, MD Knight Distinguished Professor of Neurology Washington University School of Medicine Andrew Siderowf, MD Medical Director Avid Radiopharmaceuticals 8:40 a.m. Opportunities to Advance Symptomatic Treatment of Motor and Non- motor Features Presenter: Werner Poewe, MD Director, Department of Neurology Innsbruck Medical University 1 8:55 a.m. Panel Discussion of Recommendations Moderator: Andrew Siderowf, MD Panelists: Karen Marder, MD, MPH; Werner Poewe, MD; Bernard Ravina, MD; Lisa Shulman, MD; Philip Starr, MD, PhD*; and Matthew Stern, MD* 9:15 a.m. Opportunities for Innovation in Trial Design Presenter: Christopher Coffey, PhD Professor, Department of Biostatistics University of Iowa 9:30 a.m. Panel Discussion of Recommendations Moderator: Randall Bateman, MD Panelists: Christopher Coffey, PhD; Jordan Elm, PhD; Nicholas Kozauer, MD*; Bernard Ravina, MD; Ira Shoulson, MD*; and Philip Starr, MD, PhD* 9:50 a.m. Break 10:20 a.m. Opportunities to Improve Outcome Measures in PD Research Presenter: Lisa M. Shulman, MD Professor of Neurology University of Maryland School of Medicine 10:35 a.m. Panel Discussion of Recommendations Moderator: Andrew Siderowf, MD Panelists: Jordan Elm, PhD; Nicholas Kozauer, MD*; Lisa Shulman, MD; and Caroline Tanner, MD, PhD 10:55 a.m. Opportunities for Understanding and Addressing Disease Progression Presenter: Caroline Tanner, MD, PhD Director, Clinical Research The Parkinson’s Institute 11:10 a.m. Panel Discussion of Recommendations Moderator: Randall Bateman, MD Panelists: Christopher Coffey, PhD; Karen Marder, MD, MPH; Werner Poewe, MD; Ira Shoulson, MD*; Matthew Stern, MD*; and Caroline Tanner, MD, PhD 2 11:30 a.m. Panel Discussion: Priority Ranking of Clinical Research Recommendations Moderators: Randall Bateman, MD, and Andrew Siderowf, MD Panelists: Christopher Coffey, PhD; Jordan Elm, PhD; Karen Marder, MD, MPH; Werner Poewe, MD; Bernard Ravina, MD; Lisa Shulman, MD; and Caroline Tanner, MD, PhD 12:00 p.m. Lunch 1:00 p.m. Building a Translational Pipeline for Parkinson’s Disease Therapeutics Session Chairs: John Dunlop, PhD, and Steven Finkbeiner, MD, PhD NINDS Liaisons: Margaret Sutherland, PhD, and Hao Wang, PhD Introduction John Dunlop, PhD Vice President, Neuroscience AstraZeneca Steven Finkbeiner, MD, PhD Associate Director & Senior Investigator Gladstone Institute of Neurological Disease University of California, San Francisco 1:10 p.m. Patient/Disease Stratification Presenter: John Dunlop, PhD Vice President, Neuroscience AstraZeneca 1:25 p.m. Panel Discussion of Recommendations Moderator: John Dunlop, PhD Panelists: Rudi Balling, PhD; Steven Finkbeiner, MD, PhD; John Hardy, PhD; and Dean Jones, PhD 1:45 p.m. Target Engagement and Efficacy Presenter: Dimitri Krainc, MD, PhD Professor and Chairman, Department of Neurology Northwestern University 3 2:00 p.m. Panel Discussion of Recommendations Moderator: Steven Finkbeiner, MD, PhD Panelists: John Dunlop, PhD; John Hardy, PhD; Hartmuth Kolb, PhD*; Dimitri Krainc, MD, PhD; Kalpana Merchant, PhD*; and Richard Youle, PhD 2:20 p.m. Modeling Parkinson’s Disease Pathways: Forward and Reverse Translation 2:20 p.m. Presenter: Michael Lee, PhD Professor, Department of Neuroscience University of Minnesota 2:30 p.m. Presenter: Clive Svendsen, PhD Director, Regenerative Medicine Institute Cedars-Sinai Health System, Los Angeles 2:40 p.m. Panel Discussion of Recommendations Moderator: Steven Finkbeiner, MD, PhD Panelists: Wade Harper, PhD; Michael Lee, PhD; Clive Svendsen, PhD; and Richard Youle, PhD 3:00 p.m. Break 3:20 p.m. Target Identification and Validation: Criteria for Advancement Presenter: Richard Youle, PhD Senior Investigator and Chair, Biochemistry Branch NINDS, NIH 3:30 p.m. Presenter: Wade Harper, PhD Professor of Cell Biology Harvard Medical School 3:40 p.m. Panel Discussion of Recommendations Moderator: Wade Harper, PhD Panelists: Rudi Balling, PhD; John Hardy, PhD; Dean Jones, PhD; and Dimitri Krainc, MD, PhD 4 4:00 p.m. Panel Discussion: Priority Ranking of Translational Research Recommendations Moderator: John Dunlop, PhD Panelists: Rudi Balling, PhD; Steven Finkbeiner, MD, PhD; John Hardy, PhD; Wade Harper, PhD; Dean Jones, PhD; Dimitri Krainc, MD, PhD; Michael Lee, PhD; Clive Svendsen, PhD; and Richard Youle, PhD 4:30 p.m. Parkinson’s Disease Research Evaluation: A Multi-Stakeholder Perspective Session Chair: Amy Comstock Rick, JD NINDS Liaison: Beth-Anne Sieber, PhD Introduction Amy Comstock Rick, JD Chief Executive Officer, Parkinson’s Action Network 4:35 p.m. Research Evaluation: An AAMC Initiative Ann C. Bonham, PhD Chief Scientific Officer, Association of American Medical Colleges 4:45 p.m. Panel Discussion Moderator: Amy Comstock Rick, JD Panelists: Ann C. Bonham, PhD; Story C. Landis, PhD; Bernard Ravina, MD; Todd Sherer, PhD; and David Sulzer, PhD January 7, 2014 (Day 2) 9:00 a.m. Parkinson’s Disease Biology: Moving Toward Innovative Treatments Session Chairs: Virginia M-Y Lee, PhD, and Harry T. Orr, PhD NINDS Liaisons: Katrina Gwinn, MD, and Kip Ludwig, PhD Introduction Virginia M-Y Lee, PhD Director, Center for Neurodegenerative Disease Research University of Pennsylvania Perelman School of Medicine Harry T. Orr, PhD Professor of Pathology University of Minnesota 5 9:10 a.m. Pathways and Signaling Presenter: Harry T. Orr, PhD Professor of Pathology University of Minnesota 9:25 a.m. Panel Discussion of Recommendations Moderator: Mel Feany, MD, PhD Panelists: Ted M. Dawson, MD, PhD; Harry T. Orr, PhD; and Andrew Singleton, PhD 9:55 a.m. Break 10:25 a.m. Protein Processing, Aggregation, and Spread Presenter: Virginia M-Y Lee, PhD Director, Center for Neurodegenerative Disease Research University of Pennsylvania Perelman School of Medicine 10:40 a.m. Panel Discussion of Recommendations Moderator: Robert Edwards, MD Panelists: Hilal Lashuel, PhD; Virginia M-Y Lee, PhD; and J. Paul Taylor, MD, PhD 11:10 a.m. Circuit Modification Presenter: Warren M. Grill, PhD Professor of